Stone attended two universities in Boston (Northeastern University and the University of Massachusetts) for one year each and then worked as a designer at the publisher Little, Brown and Co. In 1999–2001 he was creative director at Xanga, a blogcommunity that he had helped form. Stone was then invited by Williams to take a position at Blogger, a company developing blogging software. When Stone was hired in 2003, it had recently been purchased by Google. Stone worked there until 2005, when he left to join Williams in shaping Odeo, a podcasting company.

Stone and Williams were then approached by Dorsey, whose ideas about text messaging led the three men to develop and cofound Twitter. The service allowed users to share status updates in the form of 140-character messages known as “tweets.” After Twitter went live in 2006, Stone served as creative director for the company. It quickly became a popular social networking hub as well as a mainstream form of communication. With endorsements from corporations, celebrities, and news outlets, Twitter had by 2011 more than 100 million monthly active users, with one billion tweets being sent each week. That year Stone stepped down as creative director but continued with the company as an adviser.

In 2012 Stone began work on a new venture, Jelly, a search app in which users posted questions that were answered by others in their social network. It launched two years later. In addition, Stone served as an adviser to several Web companies. His books include Blogging: Genius Strategies for Instant Web Content (2002), Who Let the Blogs Out?: A Hyperconnected Peek at the World of Weblogs (2004), and Things a Little Bird Told Me: Confessions of the Creative Mind (2014).